Nanozymes are nanoscale materials with enzyme-mimicking catalytic properties.Nanozymes can mimic the mechanism of natural enzyme molecules.By means of advanced chemical synthesis technology,the size,shape,and surface characteristics of nanozymes can be accurately regulated,and their catalytic properties can be customized according to the specific need.Nanozymes can mimic the function of natural enzymes,including catalase(CAT),superoxide dismutase(SOD),and glutathione peroxidase(GPx),to scavenge reactive oxygen species(ROS).Reported findings have shown that nanozymes have the advantages of excellent stability,low cost,and adjustable catalytic activity,thereby showing great potential and broad prospects in the application of disease treatment.Herein,we reviewed the advances in the application of nanozymes in the treatment of joint diseases.The common clinical manifestations of joint diseases include joint pain,swelling,stiffness,and limited mobility.In severe cases,joint diseases may lead to joint destruction,deformity,and functional damage,entailing crippling socioeconomic burdens.ROS is a product of oxidative stress.Increased ROS in the joints can induce macrophage M1 type polarization,which in turn induces and aggravates arthritis.Therefore,the key to the treatment of joint diseases lies in ROS scavenging and increasing oxygen(O2)content.Nanozymes have demonstrated promising application potential in the treatment of joint diseases,including rheumatoid arthritis,osteoarthritis,and gouty arthritis.However,how to ensure their biosafety,reduce the toxicity,and increase enzyme activity remains the main challenge in current research.Precise control of the chemical composition,size,shape,and surface modification of nanomaterials is the main development direction for the future.

Objective To formulate a ZIF-8 nano mimetic enzyme conjugated with platinum metal(ZIF-8@Pt)that can scavenge reactive oxygen species(ROS)and to explore its potential applications in the treatment of rheumatoid arthritis(RA).Methods The ZIF-8@Pt nanozyme was created by in situ reduction.Characterization of the nanozyme was then performed and its ability to mimic enzymes was investigated.Cell experiments were conducted using RAW264.7 cells,which were divided into three groups,including the untreated group(UT),the positive control group receiving lipopolysaccharide(LPS),which was designated as the LPS group,and the ZIF-8@Pt group receiving ZIF-8@Pt and LPS treatment.The cell experiments were conducted to evaluate the anti-inflammatory properties of ZIF-8@Pt through scavenging intracellular ROS.On the other hand,a collagen-induced arthritis(CIA)model was induced in rats.Similar to the group designations in the cell experiments,the rats were assigned to three groups,including a healthy control group(the UT group),a positive control group receiving a local injection of PBS solution in the knee joint,which was referred to as the control group,and a treatment group receiving a local injection of ZIF-8@Pt solution in the knee joint,which was referred to as the ZIF-8@Pt group.General evaluation,imaging observation,assessment of inflammatory factors,and pathological evaluation were performed to assess the therapeutic efficacy of ZIF-8@Pt against RA.Results The in vitro experiment revealed significant difference in the levels of intracellular ROS and LPS-induced M1-type macrophage polarization between the LPS group and the ZIF-8@Pt group(P＜0.05).The in vivo experiment showed that significant difference in the levels of inflammatory factors,including interleukin-1β(IL-1β),C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),and arginase-1(Arg-1)in the knee joints of the CIA rats between the LPS group and the ZIF-8@Pt group(P＜0.05).Comparing the findings for the ZIF-8@Pt group and the control group,pathology assessment revealed that ZIF-8@Pt reduced local hypoxia and suppressed osteoclastic activity,neovascularization,and M1-type macrophage polarization(P＜0.05).Conclusion The ZIF-8@Pt enzyme mimetic inhibits macrophage inflammatory polarization by ROS scavenging,thereby improving inflammation in RA.Furthermore,the ZIF-8@Pt nanozyme improves the hypoxic environment and inhibits angiogenesis and bone destruction,demonstrating promising therapeutic efficacy for RA.

Objective To study the role of curcumin-mediated sonodynamic therapy in the treatment of malignant melanoma,and to provide a new strategy for the treatment of malignant melanoma.Methods The ultrasonic sound and vibration method was applied to coat curcumin with mouse melanoma cell membrane,thereby forming biomimetic curcumin.The morphology of biomimetic curcumin was observed by transmission electron microscope.Flow cytometry was used to analyze the effect of biomimetic curcumin in terms of in vitro targeting,apoptosis,and intracellular reactive oxygen species(ROS)production.The in vivo experiment was divided into control group,US group,turmeric group,imitation turmeric group,and imitation turmeric+US group,with 3 mice in each group.The in vivo safety of biomimetic curcumin was evaluated by HE staining.In addition,HE,CD31,Ki67,and TUNEL stainings were performed to evaluate the in vivo anti-melanoma therapeutic effect of ultrasound combined with biomimetic curcumin.Results The biomimetic curcumin had a generally uniform morphology and possessed a core-shell structure.Flow cytometry analysis performed with FlowJo showed that the biomimetic curcumin could be effectively taken up by melanoma cells.The apoptosis rate was(10.30±0.61)％in the control group,(10.41±3.13)％in the ultrasound group,(24.97±1.38)％in the curcumin group,(31.39±3.84)％in the biomimetic curcumin group,and(40.89±0.79)％in the biomimetic curcumin and ultrasound combination group.The apoptosis rate in the biomimetic curcumin and ultrasound combination group was higher than those in the other groups(P＜0.05).The results of ROS flow cytometry showed that,compared with the control group,the ultrasound group demonstrated almost no increase in the fluorescence intensity,while the other groups showed an increase in the fluorescence intensity to varying degrees.There was no significant difference in the fluorescence intensity between the biomimetic curcumin group([1.10±0.38]％)and the curcumin group([0.73±0.26]％)(P＞0.05).The fluorescence intensity of the biomimetic curcumin and ultrasound combination group([3.35±0.04]％)was higher than those of the other groups(P＜0.05).HE staining showed no obvious abnormalities in the morphology of heart,liver,spleen,lung,and kidney tissues in any of the treatment groups.HE staining showed the most significant changes in cell morphology in the biomimetic curcumin and ultrasound combination group,followed by the biomimetic curcumin group and the curcumin group.No obvious abnormalities in tumor cell morphology were observed in the ultrasound group.According to the respective results of CD31 staining,Ki67 staining,and TUNEL staining,the biomimetic curcumin and ultrasound combination group had the largest brown area,the highest number of red fluorescence,and the highest number of green fluorescence,followed by the biomimetic curcumin group and the curcumin group.Conclusion The biomimetic curcumin displays uniform morphology,a core-shell structure,and good targeting properties.When it is used in combination with ultrasound,biomimetic curcumin demonstrates a good anti-tumor therapeutic effect both in vivo and in vitro.